Hormone replacement therapy has been used for many years to delay or treat the changes that accompany menopause. However, epidemiologic and clinical research has revealed significant long-term risks and unintended side effects. Selective estrogen receptor modulator (SERM) were developed mimic the advantageous properties of estrogens without the negative side effects. Knowledge of SERMs, such as Tamoxifen and Raloxifene, has led to the development of novel drugs to treat a variety of conditions. While the success of these early SERMs is encouraging, their application is still limited and many still result in negative side effects. The critical task now presented to researchers and the pharmaceutical industry is the identification of more specific compounds with more important therapeutic applications while maximizing the risk/benefit ratio. To revolutionize this process, the Luna team proposes to develop a fluorescence resonance energy transfer (FRET)-based high throughput screening (HTS) assay for SERMs. The critical advantage of the proposed assay is direct detection with minimal false positives. Direct detection not only result in lower cost and greater efficiency in screening of new SERMs, it also presents the capability for detecting new SERMs not previously identified due to the nature of the competitive assays that are currently used. [unreadable] [unreadable]